Abstract
Growth and Remodelling (G&R) is a typical response of the heart in response to changes in cardiac load or from maladaptive pathophysiological alterations. One broadly accepted theory to explain cardiac G&R phenomena is sarcomerogenesis, which is thought to take one of two forms: (1) concentric hypertrophy (i.e. fibre thickening) or (2) eccentric hypertrophy (i.e. fibre lengthening), caused by either parallel or serial additions of the sarcomere fibres inside myocytes. The question that remains is: What may be potential growth drivers for observed hypertrophy patterns in the heart?The complexity of G&R in the heart can vary between diseases and patients and is still not entirely understood. In the presented thesis, we focused on understanding cardiac G&R in two cases of pathological growth (hypertrophic cardiomyopathy and aortic stenosis) and one case of reverse growth following aortic valve replacement. An overall approach to analysing these cases of G&R is the theory of kinematic growth by Rodriguez et al. 201, this framework is capable to introduce growth and potential residual stresses within the grown domain. Yet, the interplay between growth and residual stress is not well understood, in later chapters, we assess how these two components of G&R act together and referred to this as the compatibility component of growth. In the case of hypertrophic cardiomyopathy (HCM), for instance, growth patterns appear more complex than in other diseases, with spatial heterogeneous and anisotropic hypertrophy observed without a change in loading condition. In a later chapter, we go into detail about what type of hypertrophy may be an underlying reason for the distinctive phenotypical HCM growth pattern, by investigating three independent test cases. In contrast, the mechanical drivers for reverse growth are apparent in the case of aortic valve replacement (AVR). Following AVR procedure, the heart reacts in two distinctive ways: (1) reverse growth or (2) adverse growth. In a subsequent chapter, we analysed the underlying growth pattern in both of these cases to identify commonalities across patients, by employing either a forward or inverse modelling approach.
In summary in this thesis, we analysed three key objectives of G&R in the heart. Firstly, we investigated the impact of kinematic G&R on the compatibility of the domain, by comparing perturbations of the kinematic G&R problem with each other. Secondly, three individual hypotheses of regional hypertrophy in HCM were studied to understand the mode of growth observed. And the third objective was the classification of G&R modes noticed in AVR with positive (reverse growth) or negative (adverse growth) outcomes.
| Date of Award | 1 Sept 2023 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Jack Lee (Supervisor) & David Nordsletten (Supervisor) |